Clinically relevant GABARAP deficiency abrogates bortezomib-induced immunogenic cell death in multiple myeloma.

临床相关的 GABARAP 缺乏消除了硼替佐米诱导的多发性骨髓瘤中的免疫原性细胞死亡。

• 发表时间: 2024
• 来源期刊: Oncoimmunology
• DOI: 10.1080/2162402X.2024.2360275
• PMID: 38812570
• 文章类型: Journal Article
• 中科院分区: Q2
• 方向: 医学
• 作者列表: Zhao L,Shen Z,Kroemer G,Kepp O

关键词: Immunotherapy; autophagy; danger associated molecular pattern; phagocytosis

Mesh: Multiple Myeloma / drug therapy pathology immunology genetics metabolism; Humans; Bortezomib / pharmacology therapeutic use; Adaptor Proteins, Signal Transducing / genetics metabolism deficiency; Antineoplastic Agents / pharmacology therapeutic use; Microtubule-Associated Proteins / genetics metabolism; Apoptosis Regulatory Proteins / genetics metabolism; Immunogenic Cell Death / drug effects; Cell Line, Tumor; Autophagy / drug effects; Calreticulin / metabolism genetics

Abstract

Recently, it was revealed that the high-risk, poor-prognosis downregulation of GABA type A receptor-associated protein (GABARAP) causes a defect in both autophagy and surface exposure of calreticulin (CALR) in multiple myeloma (MM) cells responding to bortezomib. Hence, GABARAP-defective MM cells fail to undergo immunogenic cell death.

摘要

最近,据透露，高风险，GABAA型受体相关蛋白(GABARAP)的不良预后下调导致对硼替佐米有反应的多发性骨髓瘤(MM)细胞中自噬和钙网织蛋白(CALR)表面暴露的缺陷.因此，GABARAP缺陷型MM细胞不能经历免疫原性细胞死亡。